RESUMEN
Gene amplifications and deletions are common changes in human cancer cells. Previous studies indicate that the regions, where the ACHE (7q22) and BCHE (3q26.1-q26.2) genes are localized, are suffering such structural modifications in breast cancer. Therefore, the products of these genes, acetylcholinesterase and butyrylcholinesterase, respectively, are related to the process of cell differentiation and proliferation, as well as apoptosis. This study also included two other genes involved in tumorigenesis, the EPHB4 (7q22.1) and MME (3q21-27). The aim of this study was to verify amplification and/or deletion in the ACHE, BCHE, EPHB4 and MME genes in 32 samples of sporadic breast cancer. The gene alterations were detected using real-time PCR and determined by relative quantification with the standard curve method. All samples presented genetic alterations, showing a higher tendency for amplification of the ACHE (62.5% vs. 37.5%; p>0.1) and EPHB4 (53.13% vs. 46.88%; p>0.5) genes, and for deletions of the BCHE and MME genes (56.25% vs. 43.75% for both; p>0.5). A positive correlation was found between alterations in ACHE-EPHB4 and BCHE-MME pairs (r(s) = 0.5948; p = 0.0004; r(s) = 0.3581; p = 0.0478, respectively) indicating that these changes comprise a wide region. In conclusion, the results suggest that these genomic regions may contain important genes for this pathology, such as the oncogenes MET (7q31) and PIK3CA (3q26), and thus being interesting targets for future studies in breast cancer research.
Asunto(s)
Acetilcolinesterasa/genética , Neoplasias de la Mama/genética , Butirilcolinesterasa/genética , Variaciones en el Número de Copia de ADN , Neprilisina/genética , Receptor EphB4/genética , Adenocarcinoma/enzimología , Adenocarcinoma/genética , Adulto , Anciano , Neoplasias de la Mama/enzimología , Carcinoma Ductal de Mama/enzimología , Carcinoma Ductal de Mama/genética , Carcinoma Lobular/enzimología , Carcinoma Lobular/genética , Cromosomas Humanos Par 3/genética , Cromosomas Humanos Par 7/genética , ADN de Neoplasias/genética , Femenino , Proteínas Ligadas a GPI/genética , Amplificación de Genes , Eliminación de Gen , Humanos , Persona de Mediana Edad , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
OBJECTIVE: The ligand EphrinB2 and the corresponding receptor EphB4 are up-regulated and involved in tumour growth in various human cancers. However, little is known about how this receptor-ligand complex contributes to the progression of glioma. This prompted us to study the association between the expressions of EphrinB2 and EphB4, clinicopathological variables, and glioma patient outcome. METHODS: Immunohistochemical staining was performed to detect the expression patterns of EphrinB2 and EphB4 in the biopsies from 96 patients with primary gliomas. Kaplan-Meier survival and Cox regression analyses were performed to evaluate the prognosis of patients. RESULTS: Immunohistochemical analysis revealed that the expression of EphrinB2 was significantly correlated with that of EphB4 (r=0.86, p=0.002). EphrinB2 and EphB4 were significantly associated with the Karnofsky performance scale (KPS) score and World Health Organization grades of patients with gliomas, respectively. Especially, the positive expression rates of EphrinB2 and EphB4 were significantly higher in patients with higher grade (both p=0.001) and lower KPS score (p=0.002 and 0.003, respectively). Multivariate Cox regression analysis revealed that EphrinB2 and EphB4 expressions were both independent prognostic factors for progress-free survival of glioblastoma patients (both p=0.02). CONCLUSION: Our data indicated for the first time that EphrinB2 and EphB4 expressions increase according to the histopathological grade and KPS score of glioma, and their expression levels are related to the progression-free survival of glioblastoma patients.
Asunto(s)
Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/metabolismo , Efrina-B2/metabolismo , Glioma/diagnóstico , Glioma/metabolismo , Receptor EphB4/metabolismo , Adulto , Anciano , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/metabolismo , Neoplasias Encefálicas/patología , Progresión de la Enfermedad , Femenino , Glioblastoma/diagnóstico , Glioblastoma/metabolismo , Glioblastoma/patología , Glioma/patología , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Distribución TisularRESUMEN
Neurogenesis is a process influenced by environmental cues that create highly specific functional niches. Recently, the role of blood vessels in the maintenance and functioning of neurogenic niches during development and in adult life has been hallmarked. In addition to their trophic support for the highly demanding neurogenic process, blood vessels regulate neuroblast differentiation and migration and define functional domains. Since neurogenesis along the forebrain neurogenic niche (FNN) is a multistage process, in which neuroblast proliferation, differentiation and migration are spatially restricted to specific locations; we evaluated the structural features of vascular beds that support these processes during critical time points in their development. Additionally, we studied the molecular identity of the endothelial components of vascular beds using the expression of the venous marker EphB4. Our results show that blood vessels along the FNN: 1) are present very early in development; 2) define the borders of the FNN since early developmental stages; 3) experience constant remodeling until achieving their mature structure; 4) show venous features during perinatal developmental times; and 5) down-regulate their EphB4 expression as development proceeds. Collectively, our results describe the formation of the intricate vascular network that may support neurogenesis along the FNN and show that blood vessels along this neurogenic niche are dynamic entities that experience significant structural and molecular remodeling throughout development.